Methods and systems for determining and characterizing various systems and tissue properties are known. Characterization of internal tissues using non-invasive and non-traumatic techniques is challenging in many areas. Non-invasive detection of various cancers remains problematic and unreliable. Similarly, non-invasive assessment and monitoring of important internal clinical parameters, such as intracranial pressure and cardiac output, are also practical challenges, despite the efforts devoted to developing such techniques.
Ultrasound imaging is a non-invasive, diagnostic modality that is capable of providing information relating to tissue properties. In the field of medical imaging, ultrasound may be used in various modes to produce images of objects or structures within a patient. In a transmission mode, an ultrasound transmitter is placed on one side of an object and the sound is transmitted through the object to an ultrasound receiver. An image may be produced in which the brightness of each image pixel is a function of the amplitude of the ultrasound that reaches the receiver (attenuation mode), or the brightness of each pixel may be a function of the time required for the sound to reach the receiver (time-of-flight mode). Alternatively, if the receiver is positioned on the same side of the object as the transmitter, an image may be produced in which the pixel brightness is a function of the amplitude of reflected ultrasound (reflection or backscatter or echo mode). In a Doppler mode of operation, the tissue (or object) is imaged by measuring the phase shift of the ultrasound reflected from the tissue (or object) back to the receiver.
Ultrasonic transducers for medical applications are constructed from one or more piezoelectric elements activated by electrodes. Such piezoelectric elements may be constructed, for example, from lead zirconate titanate (PZT), polyvinylidene diflouride (PVDF), PZT ceramic/polymer composites, and the like. The electrodes are connected to a voltage source, a voltage waveform is applied, and the piezoelectric elements change in size at a frequency corresponding to that of the applied voltage. When a voltage waveform is applied, the piezoelectric elements emit an ultrasonic wave into the media to which it is coupled at the frequencies contained in the excitation waveform. Conversely, when an ultrasonic wave strikes the piezoelectric element, the element produces a corresponding voltage across its electrodes. Numerous ultrasonic transducer constructions are known in the art.
When used for imaging, ultrasonic transducers are provided with several piezoelectric elements arranged in an array and driven by different voltages. By controlling the phase and amplitude of the applied voltages, ultrasonic waves combine to produce a net ultrasonic wave that travels along a desired beam direction and is focused at a selected point along the beam. By controlling the phase and the amplitude of the applied voltages, the focal point of the beam can be moved in a plane to scan the subject. Many such ultrasonic imaging systems are well known in the art.
An acoustic radiation force is exerted by an acoustic wave on an object in its path. The use of acoustic radiation forces produced by an ultrasound transducer has been proposed in connection with tissue hardness measurements. See Sugimoto et al., “Tissue Hardness Measure Using the Radiation Force of Focused Ultrasound”, IEEE Ultrasonics Symposium, pp. 1377-80, 1990. This publication describes an experiment in which a pulse of focused ultrasonic radiation is applied to deform the object at the focal point of the transducer. The deformation is measured using a separate pulse-echo ultrasonic system. Measurements of tissue hardness are made based on the amount or rate of object deformation as the acoustic force is continuously applied, or by the rate of relaxation of the deformation after the force is removed.
Another system is disclosed by T. Sato, et al., “Imaging of Acoustical Nonlinear Parameters and Its Medical and Industrial Applications: A Viewpoint as Generalized Percussion,” Acoustical Imaging, Vo. 20, pg. 9-18, Plenum Press, 1993. In this system, a lower frequency wave (350 kHz) is used as a percussion force, and an ultrasonic wave (5 MHz) is used in a pulse-echo mode to produce an image of the subject. The percussion force perturbs second order nonlinear interactions in tissues, which may reveal more structural information than conventional ultrasound pulse-echo systems.
Fatemi and Greenleaf reported an imaging technique that uses acoustic emission to map the mechanical response of an object to local cyclic radiation forces produced by interfering ultrasound beams. The object is probed by arranging the intersection of two focused, continuous-wave ultrasound beams of different frequencies at a selected point on the object. Interference in the intersection region of the two beams produces modulation of the ultrasound energy density, which creates a vibration in the object at the selected region. The vibration produces an acoustic field that can be measured. The authors speculate that ultrasound-stimulated vibro-acoustic spectrography has potential applications in the non-destructive evaluation of materials, and for medical imaging and noninvasive detection of hard tissue inclusions, such as the imaging of arteries with calcification, detection of breast microcalcifications, visualization of hard tumors, and detection of foreign objects.
U.S. Pat. Nos. 5,903,516 and 5,921,928 (Greenleaf et al.) disclose a method and system for producing an acoustic radiation force at a target location by directing multiple high frequency sound beams to intersect at the desired location. A variable amplitude radiation force may be produced using variable, high frequency sound beams, or by amplitude modulating a high frequency sound beam at a lower, baseband frequency. The mechanical properties of an object, or the presence of an object, may be detected by analyzing the acoustic wave that is generated from the object by the applied acoustic radiation force. An image of the object may be produced by scanning the object with high frequency sound beams and analyzing the acoustic waves generated at each scanned location. The mechanical characteristics of an object may also be assessed by detecting the motion produced at the intersections of high frequency sound beams and analyzing the motion using Doppler ultrasound and nuclear magnetic resonance imaging techniques. Variations in the characteristics of fluids (e.g. blood), such as fluid temperature, density and chemical composition can also be detected by assessing changes in the amplitude of the beat frequency signal. Various applications are cited, including detection of atherosclerosis, detection of gas bubbles in fluids, measurement of contrast agent concentration in the blood stream, object position measurement, object motion and velocity measurement, and the like. An imaging system is also disclosed.
U.S. Pat. No. 6,039,691 (Walker et al.) discloses methods and apparatus for soft tissue examination employing an ultrasonic transducer for generating an ultrasound pulse that induces physical displacement of viscous or gelatinous biological fluids and analysis techniques that determine the magnitude of the displacement. The transducer receives ultrasonic echo pulses and generates data signals indicative of the tissue displacement. This apparatus and method is particularly useful for examining the properties of a subject's vitreous body, in connection with the evaluation and/or diagnosis of ocular disorders, such as vitreous traction.
U.S. Pat. No. 5,086,775 (Parker et al.) describes a system in which a low frequency vibration source is used to generate oscillations in an object, and a coherent or pulsed ultrasound imaging system is used to detect the spatial distribution of the vibration amplitude or speed of the object in real-time. In particular, the reflected Doppler shifted waveform generated is used to compute the vibration amplitude and frequency of the object on a frequency domain estimator basis, or on a time domain estimator basis. Applications of this system include examination of passive structures such as aircraft, ships, bridge trusses, as well as soft tissue imaging, such as breast imaging.
Several U.S. Patents to Sarvazyan relate to methods and devices for ultrasonic elasticity imaging for noninvasively identifying tissue elasticity. Tissue having different elasticity properties may be identified, for example, by simultaneously measuring strain and stress patterns in the tissue using an ultrasonic imaging system in combination with a pressure sensing array. The ultrasonic scanner probe with an attached pressure sensing array may exert pressure to deform the tissue and create stress and strain in the tissue. This system may be used, for example, to measure mechanical parameters of the prostate. U.S. Patents to Sarvazyan also describe shear wave elasticity imaging using a focused ultrasound transducer that remotely induces a propagating shear wave in tissue. Shear modulus and dynamic shear viscosity at a given site may be determined from the measured values of velocity and attenuation of propagating shear waves at that site.
Cardiac Performance
Cardiac output is important to the body for two reasons. The major limitation in the delivery of nutrients to the tissues of the body is the delivery of oxygen. Delivery of metabolic substrates (“food”) and elimination of waste products require less blood flow than is necessary for adequate delivery of oxygen for the tissues' metabolic needs. An inadequate cardiac output translates into some tissues of the body receiving too little oxygen and leads to dysfunction of the affected organ or even tissue damage or cell death of the deprived tissue.
The “gold standard” for measurement of cardiac output is the pulmonary artery catheter. It measures cardiac output via the thermodilution technique. It is effective, and not difficult to use, but it requires placing the catheter into a vein and threading the catheter through the heart and into the lungs. The risks to the patient from using the pulmonary artery catheter preclude routine use. Echocardiography can be used, either transthoracically or using esophageal echo. This technique is safer to the patient, but it is technically more difficult, less accurate, and impractical to use for longer than a few minutes at a time. Other techniques exist, but none have gained universal acceptance. A low risk method for measuring either cardiac output, or providing a good estimation of the components of cardiac output, would prove invaluable in critical care settings. Such a technique would likely be used in far more patients than is the number of patients who currently receive a pulmonary artery catheter.
Cardiac output is the product of heart rate and stroke volume (the amount of blood the heart pumps to the body in a single beat). Heart rate is easy to determine. Stroke volume is difficult to measure directly, so it is generally calculated by measuring or estimating cardiac output and then deriving stroke volume=cardiac output÷heart rate. The objective of providing a non-invasive measurement of cardiac output thus becomes a problem of how to measure stroke volume in a non-invasive fashion. Heart rate is also usually easy to manipulate. Consequently, the difficult aspect in the clinical manipulation of cardiac output is generally reduced to a problem of how to manipulate stroke volume.
Stroke volume is a function of two basic properties of the heart: volume status and contractility. Each of these parameters is as important to blood pressure as vascular resistance and heart rate. Although the volume status of a patient is manipulated by increasing or decreasing the blood volume of the body, what is really important is the volume status of the right and left ventricles. The ventricles need to be “filled up” prior to contraction for two reasons. First, the ventricles cannot pump to the lungs or body (right and left ventricles, respectively) what the ventricles don't have in them at the start of contraction. The more blood in the chamber of the ventricle, the more blood could be potentially pumped out. Second, as more blood is put in the ventricle, the muscle cells of the heart become more stretched. The greater the stretch, the harder the heart muscle contracts at the next heartbeat. This phenomenon is known as the length-tension relationship, and is illustrated in FIG. 1. Stronger contractions permit the heart to pump against a higher blood pressure and/or pump out a higher percentage of the blood in the ventricle. Expressed mathematically, stroke volume (SV) is equal to the product of end-diastolic volume (EDV, the amount of blood in the chamber of the ventricle just before contraction begins) and the ejection fraction (EF, the percent of the EDV that is pushed out of the ventricle during heart contraction). SV=EDV×EF.
When treating a patient who is thought to have a low stroke volume, a common clinical maneuver is to administer fluid. In a normal heart, the EF will not decrease even if blood pressure increases as a result of the improved stroke volume. However, a heart with poorly functioning muscle will have a low EF at baseline and will not demonstrate much of an improvement in its contraction when EDV is increased (See FIG. 1). In fact, more volume may worsen the status of the patient if the heart does not improve its performance in response to the volume. If performance does not improve, the heart may become distended, which results in impaired function. Furthermore, even if over-distention does not occur, the increase in volume increases the filling pressures, that in turn must be matched by increased pressures in the atrium and veins. In the case of the right ventricle, high venous pressures cause congestion in the abdominal organs and legs that can lead to liver and intestinal dysfunction and to peripheral edema. In the case of the left ventricle, high venous pressures cause the pressure in the blood vessels in the lungs to increase. If these pressures get too high, fluid leaks out into the lungs and causes symptoms of heart failure (shortness of breath, inability to lay flat) or even pulmonary edema, a life-threatening event where the air sacs in the lung fill with fluid and limit the ability to get oxygen into the blood.
It is therefore important to know when giving a patient more fluid would produce these undesirable side effects. Current technology for this determination largely rests with the application of the pulmonary artery catheter. The catheter can measure the pressure in the atria and thus provide an estimate of the pressure in the ventricular chamber during diastole when the heart muscle is relaxed. If these pressures are already high, then more fluid must be administered with great care, if at all. Unfortunately, interpretation of pressures provided by the pulmonary artery catheter can be difficult, making optimal fluid management problematic. The difficulty, in part, is that the relationship between the filling pressure (end-diastolic pressure) and volume (end-diastolic volume) is not linear. FIG. 2 illustrates this relationship between end-diastolic pressure and volume for heart tissue that is stiff and compliant. A change in pressure of a few mmHg could represent a big or a small change in ventricular volume, depending on the character of the heart tissue. Furthermore, as the condition of the heart changes, the curve can shift around making it harder to interpret the pressure measurements as a measure of end-diastolic volume.
Ideally, clinicians would like to have a direct measure of end-diastolic volume. An echocardiogram may provide a volume measurement, but this measurement does not tell the clinician whether that volume is too high, too low or just right. Measurement of ventricular wall stiffness, if it could be provided, would be helpful because wall stiffness is directly affected by ventricular pressure. In fact, knowledge of a wall stiffness parameter may be more useful than knowledge of a pressure parameter because stiffness is also affected by ventricular size. Measurement of a ventricular wall stiffness parameter is likely to be more effective than measurement of a pressure parameter in determining when fluid volume administration will be ineffective or even harmful to a patient.
Ultrasound techniques, such as Doppler tissue imaging modes, have recently been proposed for use in the diagnosis of cardiac tissue and function. In general, these techniques involve tracking of tissue movement, or velocity. Tissue velocities are used to derive an estimate of strain rate, and from strain rate, an estimation of tissue strain may be derived. These techniques are dependent on accurate tissue motion estimates, when tissues are moving in different directions within a small spatial region.
U.S. Pat. No. 6,527,717 discloses systems and methods for analyzing tissue motion in which motion estimates are corrected for transducer motion. Tissue motion may be used to determine a strain rate or strain, and motion estimates may be generated using data acquired by an intracardiac transducer array.
U.S. Pat. No. 6,099,471 discloses ultrasound techniques for determining strain velocity from tissue velocity. Tissue velocity is determined based on measurements of the pulse-to-pulse Doppler shift at positions along an ultrasound beam.
U.S. Pat. No. 6,517,485 discloses ultrasound systems and methods for calculating and displaying tissue deformation parameters, such as tissue Doppler and strain rate imaging. U.S. Pat. No. 6,537,221 relates to strain rate analysis for ultrasound images in which the spatial gradient of velocity is calculated in the direction of tissue motion. U.S. Pat. No. 6,579,240, discloses ultrasound display of a moving structure, such as a cardiac wall tissue within a region of interest, as a color representation.
The accuracy and clinical usefulness of tissue strain predictions based on the estimation of strain rate from Doppler tissue velocities is problematic. Existing methods of measuring ventricular filling and cardiac contractility using intra-arterial lines or echocardiograms have limited application because of the risk to the patient, high expense and difficulty in interpretation of the information provided. Lack of direct, non-invasive and inexpensive methods to measure ventricular filling and cardiac contractility means that optimal management of stroke volume is missing from the care of many patients who would benefit from such optimization.
Arterial Blood Pressure
Arterial blood pressure (ABP) is a fundamental objective measure of the state of an individual's health. Indeed, it is considered a “vital sign” and is of critical importance in all areas of medicine and healthcare. The accurate measure of ABP assists in determination of the state of cardiovascular and hemodynamic health in stable, urgent, emergent, and operative conditions, indicating appropriate interventions to maximize the health of the patient.
Currently, ABP is most commonly measured noninvasively using a pneumatic cuff, often described as pneumatic plethysmography or Korotkoff's method. While this mode of measurement is simple and inexpensive to perform, it does not provide the most accurate measure of ABP, and it is susceptible to artifacts resulting from the condition of arterial wall, the size of the patient, the hemodynamic status of the patient, and autonomic tone of the vascular smooth muscle. Additionally, repeated cuff measurements of ABP result in falsely elevated readings of ABP, due to vasoconstriction of the arterial wall. To overcome these problems, and to provide a continuous measure of ABP, invasive arterial catheters are used. While such catheters are very reliable and provide the most accurate measure of ABP, they require placement by trained medical personnel, usually physicians, and they require bulky, sophisticated, fragile, sterile instrumentation. Additionally, there is a risk of permanent arterial injury causing ischemic events when these catheters are placed. As a result, these invasive monitors are only used in hospital settings and for patients who are critically ill or are undergoing operative procedures.
U.S. Pat. No. 4,869,261 to Penaz discloses a method for automatic, non-invasive determination of continuous arterial blood pressure in arteries compressible from the surface by first determining a set point with a pressure cuff equipped with a plethysmographic gauge of vascular volume and then maintaining the volume of the measured artery constant to infer arterial blood pressure. A generator producing pressure vibrations superimposed on the basic blood pressure wave, and the changes in the oscillations of the blood pressure wave are monitored by an active servo-system that constantly adjusts the cuff pressure to maintain constant arterial volume; thus, the frequency of vibration of the blood pressure wave that is higher than the highest harmonic component of the blood pressure wave is used to determine arterial blood pressure.
U.S. Pat. No. 4,510,940 to Wesseling discloses a method for correcting the cuff pressure in the indirect, non-invasive and continuous measurement of the blood pressure in a part of the body by first determining a set-point using a plethysmograph in a fluid-filled pressure cuff wrapped around an extremity and then adjusting a servo-reference level as a function of the shape of the plethysmographic signal, influenced by the magnitude of the deviation of the cuff pressure adjusted in both open and closed systems.
U.S. Pat. No. 5,241,964 to McQuilkin discloses a method for a non-invasive, non-occlusive method and apparatus for continuous determination of arterial blood pressure using one or more Doppler sensors positioned over a major artery to determine the time-varying arterial resonant frequency and hence blood pressure. Alternative methods including the concurrent use of proximal and distal sensors, impedance plethysmography techniques, infrared percussion sensors, continuous oscillations in a partially or fully inflated cuff, pressure transducers or strain gauge devices applied to the arterial wall, ultrasonic imaging techniques which provide the time-varying arterial diameter or other arterial geometry which changes proportionately with intra-mural pressure, radio frequency sensors, or magnetic field sensors are also described.
U.S. Pat. No. 5,830,131 to Caro et al. discloses a method for determining physical conditions of the human arterial system by inducing a well-defined perturbation (exciter waveform) of the blood vessel in question and measuring a hemo-parameter containing a component of the exciter waveform at a separate site. The exciter consists of an inflatable bag that can exert pressure on the blood vessel of interest, and is controlled by a processor. Physical properties such as cardiovascular disease, arterial elasticity, arterial thickness, arterial wall compliance, and physiological parameters such as blood pressure, vascular wall compliance, ventricular contractions, vascular resistance, fluid volume, cardiac output, myocardial contractility, etc. are described.
U.S. Pat. No. 4,646,754 to Seale discloses a method for non-invasively inducing vibrations in a selected element of the human body, including blood vessels, pulmonary vessels, and eye globe, and detecting the nature of the responses for determining mechanical characteristics of the element. Methods for inducing vibrations include mechanical drivers, while methods for measuring responses include ultrasound, optical means, and visual changes. Mechanical characteristics include arterial blood pressure, organ impedance, intra-ocular pressure, and pulmonary blood pressure.
U.S. Pat. No. 5,485,848 to Jackson et al. discloses a method and apparatus for non-invasive, continuous arterial blood pressure determination using a separable, diagnostically accurate blood pressure measuring device, such as a conventional pressure cuff, to initially calibrate the system and then measuring arterial wall movement caused by blood flow through the artery to determine arterial blood pressure. Piezoelectric devices are used in wristband device to convert wall motion signals to an electric form that can be analyzed to yield blood pressure.
U.S. Pat. No. 5,749,364 to Sliwa, Jr. et al. discloses a method and apparatus for the determination of pressure and tissue properties by utilizing changes in acoustic behavior of micro-bubbles in a body fluid, such as blood, to present pressure information. This invention is directed at the method of mapping and presenting body fluid pressure information in at least two dimensions and to an enhanced method of detecting tumors.
PCT International Patent Publication WO 00/72750 to Yang et al. discloses a method and apparatus for the non-invasive, continuous monitoring of arterial blood pressure using a finger plethysmograph and an electrical impedance photoplethysmograph to monitor dynamic behavior of arterial blood flow. Measured signals from these sensors on an arterial segment are integrated to estimate the blood pressure in this segment based on a hemodynamic model that takes into account simplified upstream and downstream arterial flows within this vessel.
A noninvasive, continuous ABP monitor would provide medical personnel with valuable information on the hemodynamic and cardiovascular status of the patient in any setting, including the battlefield, emergency transport, clinic office, and triage clinics. Additionally, it would provide clinicians the ability to continuously monitor the ABP of a patient in situations where the risks of an invasive catheter are unwarranted or unacceptable (e.g., outpatient procedures, ambulance transports, etc.). Thus, the present invention is directed to methods and systems for the continuous assessment of ABP using non-invasive ultrasound techniques.